CORE A FSHD BIORESOURCES CORE No pathogenic gene(s) have been identified in FSHD and the molecular and cellular pathophysiology remains unclear. Moreover, the complex genetic and epigenetic changes have precluded the development of a representative animal model. Consequently, access to large numbers of well-characterized, patient-derived biological samples remains vital in advancing FSHD research. The overall aim of the proposed FSHD Bioresources Core is to generate wellcharacterized biological resources, collected in a standardized way and that will assist the Program Project's four proposed scientific studies achieve their proposed aims. To this end we will generate sets of biological resources from a) FSHDl subjects, b) FSHD2 (phenotypic) subjects and c) normal control subjects. Each set will include a flash-frozen muscle sample, a myoblast cell line and a skin-derived fibroblast cell line. Each subject will be comprehensively genotyped for the FSHD region and clinically characterized for overall disease severity, strength of the muscle group from which the sample is derived as well as pathologic grading of an adjacent muscle biopsy sample.

Public Health Relevance

This core will enhance the capability of a nascent FSHD biorepository in Rochester and will allow the collection of enough biological resources to serve not only the needs of the proposed Program Project but the needs of the wider FSHD research community as well.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS069539-05
Application #
8634149
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98109
Hendrickson, Peter G; Doráis, Jessie A; Grow, Edward J et al. (2017) Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons. Nat Genet 49:925-934
Campbell, Amy E; Oliva, Jonathan; Yates, Matthew P et al. (2017) BET bromodomain inhibitors and agonists of the beta-2 adrenergic receptor identified in screens for compounds that inhibit DUX4 expression in FSHD muscle cells. Skelet Muscle 7:16
Jagannathan, Sujatha; Bradley, Robert K (2017) Congenital myotonic dystrophy-an RNA-mediated disease across a developmental continuum. Genes Dev 31:1067-1068
Feng, Qing; Jagannathan, Sujatha; Bradley, Robert K (2017) The RNA Surveillance Factor UPF1 Represses Myogenesis via Its E3 Ubiquitin Ligase Activity. Mol Cell 67:239-251.e6
Lemmers, Richard Jlf; van der Vliet, Patrick J; Balog, Judit et al. (2017) Deep characterization of a common D4Z4 variant identifies biallelic DUX4 expression as a modifier for disease penetrance in FSHD2. Eur J Hum Genet :
Shadle, Sean C; Zhong, Jun Wen; Campbell, Amy E et al. (2017) DUX4-induced dsRNA and MYC mRNA stabilization activate apoptotic pathways in human cell models of facioscapulohumeral dystrophy. PLoS Genet 13:e1006658
Mason, Amanda G; Slieker, Roderick C; Balog, Judit et al. (2017) SMCHD1 regulates a limited set of gene clusters on autosomal chromosomes. Skelet Muscle 7:12
van den Boogaard, Marlinde L; Lemmers, Richard J F L; Camaño, Pilar et al. (2016) Double SMCHD1 variants in FSHD2: the synergistic effect of two SMCHD1 variants on D4Z4 hypomethylation and disease penetrance in FSHD2. Eur J Hum Genet 24:78-85
Mul, Karlien; van den Boogaard, Marlinde L; van der Maarel, Silvère M et al. (2016) Integrating clinical and genetic observations in facioscapulohumeral muscular dystrophy. Curr Opin Neurol 29:606-13
Knopp, Paul; Krom, Yvonne D; Banerji, Christopher R S et al. (2016) DUX4 induces a transcriptome more characteristic of a less-differentiated cell state and inhibits myogenesis. J Cell Sci 129:3816-3831

Showing the most recent 10 out of 45 publications